Medical system

ABSTRACT

Implantable drug delivery system comprising a reservoir module provided with a drug reservoir and a drug expelling means arranged to expel a drug from said drug reservoir, and a dispenser module comprising drug delivery means having a predetermined number of drug delivery openings for delivering a drug, received from said drug reservoir, to tissue. The modules are physically separate parts and the reservoir module is provided with a first connecting means and the dispenser module is provided with a second connecting means, wherein, at the time of implantation, the modules are adapted to be connected together by the first and second connecting means.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to an implantable drug delivery system, adispenser module, a set of dispensing modules, a reservoir module, a setof reservoir modules and a method of administrating a drug using theimplantable drug delivery system according to the preamble of theindependent claims.

BACKGROUND OF THE INVENTION

1. Field of the Invention

Pharmaceutical drugs can be administrated to patients in many differentways, such as orally, nasally, through electroporation or by injections.Injections can be intravenous, intramusculaire or subcutaneous. The wayof administration of drugs to a patient is often depending on propertiesof the drug, the organ to be treated and the patient's physical andsocial presumptions to control the prescribed treatment. The efficiencyof the prescribed drug treatment is also highly dependent on thepatient's abilities to follow the prescription. It is a well-known factthat the ability to follow a prescription is related to the patient'sunderstanding and knowledge of his disease and his possibility to followthe prescribed form of treatment.

Medical treatment by subcutaneous injections during a long period oftime in patients that due to physical or social reasons themselvescannot make the injection are requiring assistance from e.g. a nurse ora relative.

The injection itself might have considerable side effects because arelatively high concentration of an active substance is administrated toone local site beneath the skin. Irritation of the skin or localhaematoma is common for some patients.

Parameters that affect how frequent the injections are taken are thesubcutaneaous half-life time for the drug, i.e. the time it takes forhalf the injected dose to be absorbed by tissue, the actual dose and ofcourse the patient's ability to follow the prescription.

The injected volume depends on the type of drug used and the wantedeffect of the treatment and is normally between 0,2-0,6 ml per day givenin 1-3 injections.

The costs to offer sterilized injection syringes and to discard themafter use is a considerable part of the total cost for the treatment.

2. Description of the Prior Art

Implantable infusion pumps are well known in the art for administratingdrugs to a patient, e.g. to administer insulin to the pancreas,pain-relieving drugs to the spinal canal or intravenous administrationof drugs against Parkinson's disease. Below is a short summery ofdifferent kinds of implantable infusion pumps

U.S. Pat. No. 4,193,397 discloses an implantable infusion apparatus andmethod. Although mentioned the possibility of having a battery poweredelectrical valve to perform the pumping action, a preferred pumpembodiment employs a valve that can be actuated extracorporeally eithermanually or magnetically. Modifying the flow rates and volumes of theapparatus components, particularly the mixing chamber and the apparatusoutlet tube, can provide a dosage profile tailored to the patient'srequirements. The described embodiment requires the patient'scontribution that, according to the discussion above, is a majordrawback.

Also U.S. Pat. No. 5,769,823 discloses an implantable infusion pump. Thepurpose of this known device is primarily to provide an inexpensivelymanufacturable infusion pump. This is accomplished by arranging aplastic casing with a bellows that receives a propellant producing avapour pressure that exerts a pressure on two resilient bags containinga medicament. When a throttle means is opened a clearly defined quantityof the medicament passes out of the bags into a catheter and into thebody of a patient.

U.S. Pat. No. 4,673,391 discloses a micropump disposed within a humanbody for continuously delivering small quantities of a pharmaceuticalliquid stored therein to be injected in a human body. The control partof the pump is placed outside the body and generates a magnetic forcethat can open a valve of the implanted micropump and release thepharmaceutical liquid. A problem with this known device is that itrequires that the patient actively controls the device, which not alwaysis possible or desirable.

U.S. Pat. No. 5,752,930 relates to an implantable infusion pump foradministration of a pharmaceutically active agent via a catheter to aplurality of infusion sites located at spaced intervals in a portion ofa body to be treated by the agent. The catheter is provided with elutionholes to perform the administration of the agent. However, experiencehas shown that the flow rate of the agent is not uniform through allelution holes. In particular, at low flow rates, fluid moving down thecatheter exits the catheter at the elution hole having the least fluidresistance to flow to that relatively little or no fluid exits thecatheter through the remaining elution holes. This results in overdoseto some sites (the elution hole with the least fluid resistance) andunderdose to other sites (remaining elution holes). The device describedin U.S. Pat. No. 5,752,930 is directed to solve that problem. Thesolution is shortly to apply a first pressure to the agent in thecatheter for a first time period and a second pressure to the agent fora second time period so that substantially the same dosage of agent canbe applied to each of the sites. One drawback with this solution is thatit is technically rather complicated in that it requires an accuratecontrol of the applied pressure.

One major drawback with implantable infusion pumps according to theprior art is that they cannot easily be optimized with regard toflow-rate of the delivered drug and the volume of drug stored in thepump.

Another drawback with the prior art infusion pumps is that they have acomplicated structure inter alia due to that they all administer thedrug via a catheter.

SUMMERY OF THE INVENTION

It is an object of the present invention to provide an implantable drugdelivery system where the above-mentioned drawbacks are avoided. Thesedrawbacks are avoided by the implantable drug delivery system, adispenser module, a set of dispensing modules, a reservoir module, a setof reservoir modules and a method of administrating a drug using theimplantable drug delivery system according to the independent claims.Preferred embodiments are set forth in the dependent claims.

The present invention makes it possible to tailor the treatment bychoosing a reservoir module and a dispenser module having a desiredperformance for achieving an optimal treatment, i.e. the possibility toadminister a prescribed dose during a prescribed time in a controlledmanner.

The invention is especially useful for short term implantation foradministration of drugs during some weeks or month after a surgery, e.g.related to hip or knee prosthesis, when the patient is immobilizedduring the recovery period.

The drug is delivered to tissue through drug delivery openings that arearranged around the periphery of the dispenser module. At least twoopenings are provided. In order to provide an easy-handled implantableinfusion system the drug delivery openings are arranged around theperiphery of the implant. This is advantageous in that no deliverycatheter is needed according to a preferred embodiment of the invention.

By arranging several openings a most advantageous drug delivery isachieved in that only a limited volume is delivered at each locationwhich is favorable in that the risk of negative effect on tissue as aresult of too high drug exposure is almost eliminated. An idealsituation exists if the limited volume delivered from one opening is ina one to one relationship with the absorption at the delivery site. Inother word if the capillary force of the tissue at the delivery siteprovides for continuous absorption of all delivered drug at the deliverysite then the ideal situation occurs. Furthermore, according to stillanother embodiment of the invention, it is possible to only use some ofthe delivery openings and according to predetermined pattern “activate”different openings at different times.

The drug supplying means comprises drug delivery channels, which is asystem of channels for providing the delivery openings with drug. In animplantable drug delivery system it is of greatest importance to knowthe exact volume of the delivered drug dose. However, in a system with adrug delivery channel having several openings of the same size arrangedalong a channel with the same inner diameter along the channel thepressure inside the channel changes along the channel. This pressurechange results in a gradually decreasing delivered volume whenapproaching the distal end of the channel (the end most far from thedrug reservoir). In order to arranged a system where the deliveredvolume is controllable and almost the same for all openings the area ofthe openings increases along the channel towards the distal endaccording to a predetermined relationship.

It is also possible to arrange a separate delivery channel for eachdelivery opening. In that case and if they have the same length then thearea of the separate openings can be same resulting in that the samevolume is delivered from each opening.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a schematic drawing of the implantable system illustratingthe functional principles of the present invention;

FIG. 2 shows a cross-sectional view of the reservoir module according tothe present invention;

FIG. 3 shows cross-sectional view of the reservoir nipple according tothe present invention;

FIG. 4 shows a side view of the reservoir nipple according to thepresent invention;

FIG. 5 shows a schematic drawing illustrating a delivery channelaccording to one embodiment of the invention;

FIG. 6 shows a cross-sectional view of a connecting nipple of thedispenser module according to the present invention;

FIG. 7 shows a top view of the dispenser module according to a preferredembodiment of the invention;

FIG. 8 shows a detail of a delivery opening,according to a preferredembodiment of the invention;

FIG. 9 shows a cross-sectional view of an alternative embodiment of aconnecting nipple of the dispenser module according to the presentinvention;

FIG. 10 shows a cross-sectional view of a second alternative embodimentof a connecting nipple of the dispenser module according to the presentinvention;

FIG. 11 shows a top view of the dispenser module according to a secondpreferred embodiment of the present invention; and

FIG. 12 shows a detail of delivery openings according to a secondpreferred embodiment of the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The functional principles of the present invention are illustrated bythe schematic drawing disclosed in FIG. 1. FIG. 1 shows a reservoirmodule 1 provided with first connecting means 2 and a dispenser module 3provided with second connecting means 4. Drug delivery openings 5 arearranged along the periphery of the dispenser module. The arrowschematically designates the flow of drug from the reservoir module tothe delivery openings of the dispenser module. The modules arephysically separate parts that, at the time of implantation, are adaptedto be connected together by the first and second connecting means.

FIG. 2 shows a cross-sectional view of the reservoir module according toa preferred embodiment of the present invention. The reservoir module 1comprises a drug reservoir 10 with a reservoir opening provided with adrug supplying means which in this embodiment is illustrated as a nippleincluding an interior valve 11, drug expelling means 12,13 and aprotective casing 14 enclosing the reservoir and the expelling means.The drug supplying means supplies the dispenser module with apharmaceutical drug as will be described in greater detail below. Theprotective casing is made from an inert material having biocompatiblecharacteristics, such as titanium, stainless steel or a composite ofpolymers. The drug reservoir 10 is compressible and elastic and made ofan inert treated aluminum-laminated foil, rubber, silicone or a polymere.g. PVC. The material used inside the reservoir is of course approvedby the authorities for use in contact with each pharmaceutical drug tobe stored. The drug expelling means 12,13 can be arranged in manydifferent ways. The main function of the drug expelling means is toexert a force on the drug reservoir so that drug is expelled therefrom.One preferred way of achieving the necessary force is illustrated inFIG. 2. One or many movable plate(s) are arranged to provide a pressureon the drug reservoir. The pressure that makes the plates to move are inturn generated by a number of springs that provide for a constantmechanical force on the plate(s). As can be seen from the figure, bothhelix-wounded springs and spring leaves can be used. Also temperaturedependent bimetal springs or a foam rubber are possible to use. Anotherpossibility, as shown in the prior art, see e.g. the above-mentionedU.S. Pat. No. 4,673,391 or U.S. Pat. No. 5,769,823, is to use a liquidor a gas to exert the pressure on the reservoir.

With references to FIGS. 3 and 4 the reservoir nipple including aninterior valve will now be described.

The reservoir nipple is manufactured in an inert material, as titanium,glass, gold or a gold/platinium plated material or a polymer e.g. PVC,with a threaded outside 15 and with two stop protrusions 16, thatprevent unscrewing the reservoir module from the dispenser module whenconnected together. The reservoir nipple further comprises a profiledarea 17 to fixate the collapsible inner reservoir around by a shrinkingprocess, a supporting area 18 where the protective casing is attached bywelding, a valve 19 with two suspended claws 20 in the low end of thevalve. The top of the nipple is angled so that an injection needle canbe guided towards the upper part of the valve 21. On the lower part ofthe nipple two grooves 22,23 are made to create two distinct positionsfor the valve's suspended claws. The inner reservoir, prior to beingfilled for the first time, is free of air e.g. in vacuum, as the valveis locked into its upper position where the valve is closed (this upperposition shown in FIG. 3). The valve is locked in this position by thefriction of the suspended claws to the upper groove, which friction ishigher than surrounding air pressure allowing no air to enter the innerreservoir. When filling is about to take place, the injection needlepushes the valve to its lower position, in which the valve is open, andthe suspended claws attach to the lower groove, allowing the vacuumpressure to assist in filling the inner reservoir to its fullest extend.

It is important to have the possibility to control the valve fromoutside the body when the device is implanted, i.e. to be able to closethe valve in order to stop the liquid distribution and also to reopen itwhen desired.

One way to control the valve is by arranging a magnet into the valve 24making it possible with the aid of a strong external magnet to close, ifneeded, the distribution of liquid from the inner reservoir. Analternative method of closing liquid distribution after implantation isto have the valve mounted on a central bar equipped with a spiralspring. This bar has one thread with one stable position where the valveis open to allow liquid to flow to the dispenser module. By pushing thevalve with the tip of an injection needle the valve is brought out ofits stable position closing the liquid flow. The principle is analogousto how a ball pen with a push function works. A second push by aninjection needle allows the valve to enter its stable position, wherebythe flow can continue after a temporary stop.

As described in connection with FIG. 1 is the reservoir module connectedto the dispenser module by first and second connecting means. As brieflydiscussed above is the drug supplying means arranged in the reservoirmodule and adapted to be coupled to the dispenser module in order tosupply the dispenser module with the drug from the reservoir module.According to a preferred embodiment of the present invention (asdescribed with references to FIGS. 2-4) is the first and secondconnecting means integrated with the drug supplying means. It is ofcourse also possible to arrange the first and second connecting meansseparate from the drug supplying means (as indicated in FIG. 1).

The drug supplying means is connected to drug delivery channels in orderto deliver the drug to the openings of the dispenser module. In order toarranged a system where the delivered volume is controllable andpreferably the same for all openings the area of the openings increasesalong the channel towards the distal end according to a predeterminedrelationship. This is roughly disclosed in FIG. 5 where the deliverychannel 6 and drug delivery openings 5 are shown. As can be seenincreases the area of the openings along the channel in the direction ofthe drug flow (see arrow in the figure).

It is also possible to arrange a separate delivery channel for eachdelivery opening. In that case and if the channels have the same lengththen the area of the separate openings can be same resulting in that thesame volume is delivered from each opening.

According to a preferred embodiment of the invention is a combination ofthe above-mentioned principles of arranging the delivery channel used.

A preferred embodiment of the dispenser module according to the presentinvention provided with connecting means integrated with the drugsupplying means and also provided with preferred arrangements ofdelivery channels will know be described with references to FIGS. 6-8.FIG. 6 discloses a cross-sectional view of a connecting nipple 25 of thedispenser module 3. This connecting nipple is adapted to cooperate withthe nipple on the reservoir module and is preferably threaded and madein the same material as the reservoir nipple. Two stop protrusions 26are arranged for engagement with the corresponding protrusions 16 on thereservoir module in order to prevent the dispenser and reservoir modulesto be disconnected when once connected together. Two parallel plates 27are joined together so that the drug delivery channels are providedbetween these plates. There are many different ways to provide apredetermined grooved pattern in each plate that corresponds to thedesired delivery channels. These are etching, engraving, cutting orsimilar processes. The plates are preferably made of titanium, gold,ceramic material, silicon, stainless steel or a polymer, e.g. PVC. Theconnecting nipple 25 also comprises a membrane block 28 with twomembranes 29 made of an inert material attached to the membrane block byshrinkage fit. The above-mentioned different parts forming theconnecting nipple are welded together under pressure in order to preventany leakage in the assembled implanted system. The lower side of theconnecting nipple is provided with a lower supporting part 30 to supporta lower protecting casing 50 of the dispenser module. Similarly, theupper side of the connecting nipple is provided with an upper supportingpart 31 to support an upper protecting casing 51 of the dispensermodule. The upper and lower casings are made of an inert material andare fastened to the connecting nipple by e.g. welding. FIG. 7 shows atop view of the dispenser module according to a preferred embodiment ofthe invention. Four drug delivery openings 5 are arranged evenlydistributed along the periphery of the dispenser module. Four deliverychannels, indicated by dotted lines, supply the openings with a drugliquid. The upper membrane of the two membranes 29 is also disclosed. Inorder to guide the tip of a syringe when filling or refilling theimplant with a drug two magnets 33 are arranged on the upper side of thedispenser module, either integrated in the connecting nipple or in theupper protective casing. A detector that detects the magnet fields fromthe magnet is connected to an apparatus for guiding the tip of thesyringe to the correct position above the membrane 29.

FIG. 8 shows in great detail one of the delivery openings according thepreferred embodiment of the present invention. The joined plates 27extend outside the upper and lower protecting casing 50,51. One of theplates 35 is bent around the rounded end of the other plate so that theoutflow opening 36 is protected against pressure from the tissue thatmight reduce or stop the outflow. The outflow is arranged at the peak ofthe rounded end of the other plate in order to avoid that drug liquid isaccumulated around the outflow opening 36.

An alternative embodiment of the dispenser module according to thepresent invention provided with connecting means integrated with thedrug supplying means and also provided with preferred arrangements ofdelivery channels will know be described with references to FIGS. 9-12.

FIG. 9 discloses a cross-sectional view of a connecting nipple of thedispenser module. This connecting nipple is adapted to cooperate withthe nipple on the reservoir module and is preferably threaded and madein the same material as the reservoir nipple. Two stop protrusions 26′are arranged for engagement with the corresponding protrusions 16 on thereservoir module in order to prevent the dispenser and reservoir modulesto be disconnected when once connected together. The connecting nipplealso comprises a membrane block 28′ with two membranes 29′ made of aninert material attached to the membrane block by shrinkage fit 32′. Theabove-mentioned different parts forming the connecting nipple are weldedtogether under pressure in order to prevent any leakage in the assembledimplanted system. The lower side of the connecting nipple is providedwith a lower supporting part 30′ to support a lower protecting casing50′ of the dispenser module. Similarly, the upper side of the connectingnipple is provided with an upper supporting part 31′ to support an upperprotecting casing 51′ of the dispenser module. The upper and lowercasings are made of an inert material and are fastened to the connectingnipple by e.g. welding. The embodiment described in connection with FIG.9 differs from the one described in connection with FIG. 6 in that aconnection 56 is provided, e.g. on the side of the connection nipple,where a pump (not shown) is arranged instead of a direct connection of adelivery channel (formed e.g. by plates 27 in FIG. 6). The pump receivesvia opening 56 a flow of drug liquid from the reservoir module and is onits other side (downstream) connected to delivery channels, e.g. formedby plates as in FIGS. 6-8.

FIG. 10 discloses a cross-sectional view of a connecting nipple of stillanother alternative embodiment of the dispenser module. In addition tothe connecting nipple described in connection with FIG. 9 an additionalconnection 58 is arranged, e.g. on the side of the nipple, forconnection of a second pump. This pump is activated when filling orrefilling the reservoir module.

FIG. 11 shows a top view of the dispenser module according to a secondpreferred embodiment of the invention. Several delivery openings 5 arearranged along the periphery of the dispenser module. A drug supplyingchannel 60 runs along the periphery, close to the delivery openings, ofthe dispenser module in order to supply the openings with a drug liquid.This drug supplying channel is provided with the drug liquid from thereservoir module. This can be performed by connecting the periphery drugsupplying channel 60 to the channel(s) formed by the plates 27 asdescribed in connection with FIG. 6. Alternatively it is connected toone or many pumps 38 as illustrated in FIG. 11. The embodiment disclosedin FIG. 11 further comprises a control unit 37, a power supply 41, e.g.a battery, and one or many valves 39. A separating wall 40 is arrangedto separate the “wet” part of the module from the control unit and thepower supply. A connection part 33 for connection of a sensor or a heartstimulating electrode (e.g. according to the IS-standard) can also bearranged on the dispenser module.

FIG. 12 shows in greater detail the delivery openings according theembodiment of the present invention described in FIG. 11. The rightdrawing shows a cross-sectional view of the periphery drug supplyingchannel 60 and three delivery openings. The left drawing shows across-sectional view of a delivery opening along line A—A of the rightdrawing.

The periphery drug supplying channel 60 and the delivery openings arepreferably arranged inside a plate arrangement running along theperiphery of the module. The plate arrangement comprises two joinedplates 31 that are joined together so that the periphery drug deliverychannel 60 and the outflow channels 34 to the delivery openings 36 areprovided between these plates. There are many different ways to providea predetermined grooved pattern in each plate that correspond to thedesired delivery channels. These are etching, engraving, cutting orsimilar processes. The plates are preferably made of titanium, gold,ceramic material, silicon, stainless steel or a polymer, e.g. PVC. Oneof the plates 35 is bent around the rounded end of the other plate sothat the outflow opening 36 is protected against pressure from thetissue that might reduce or stop the outflow. The outflow is arranged atthe peak of the rounded end of the other plate in order to avoid thatdrug liquid is accumulated around the outflow opening 36. The outflowchannels 34 from the periphery drug supplying channel to the deliveryopenings are provided with an increasing cross-sectional area dependingon the distance from reservoir module in order to be able to deliver thesame volume from each delivery opening (see description in connectionwith FIG. 5).

Below is a description of a method of using an implantable drug deliverysystem according to the present invention.

Depending of the therapy prescribed to a patient, e.g. the treatmentduration, social situation for the patient, the prescribed dosage, etc.,a matching pair of reservoir and dispenser modules is chosen. The drugoutflow per time unit for a particular dispenser module can becalculated based on the number of delivery openings, the cross-sectionalarea of the drug delivery channels and the viscosity for the drugliquid. The higher dosing volume the more delivery openings in order tominimize the dosing volume delivered at each opening per time unit. Thecross-sectional area of an outflow channel is typically in the range of0,01 mm to 0,1 mm. The flow-rate of the dispenser module is typically inthe range of 8-12 μl/hour. The volume of the inner reservoir istypically in the range 4-30 ml.

The dispenser module is connected to the reservoir module via thethreaded nipples by rotating the modules relative each other until thestop protrusion engages. A needle of a syringe, filled with a drug,penetrates the membranes of the dispenser module and opens the valve bymoving valve part 19 to its lower position. The inner reservoir of thereservoir module is then filled due to the under-pressure exerted by thevacuum inside the inner reservoir. When the inner reservoir is filledwith a drug, the drug expelling means, e.g. plates and one or manysprings, exert a force on the inner reservoir that increases thepressure inside the reservoir. The inner reservoir then expels the drugliquid to the drug delivery channels of the dispenser module and thus tothe tissue near the implanted system. This situation persists until theinner reservoir is so compressed that the pressure inside the reservoiris less than the counter pressure from the tissue near the deliveryopenings. It is then possible to refill the reservoir module and theabove procedure is repeated.

The present invention is not limited to the above-described preferredembodiments. Various alternatives, modifications and equivalents may beused. Therefore, the above embodiments should not be taken as limitingthe scope of the invention, which is defined by the appending claims.

What is claimed is:
 1. Implantable drug delivery system comprising areservoir module provided with a drug reservoir and a drug expellingmeans arranged to expel a drug from said drug reservoir to a dispensermodule for delivering the drug to tissue, characterized in that saidmodules are physically separate parts and that said reservoir module isprovided with a first connecting means and said dispenser module isprovided with a second connecting means, wherein, at the time ofimplantation, said reservoir and dispenser modules are adapted to beconnected together by said first and second connecting means.
 2. Systemaccording to claim 1 characterized in that said first connecting meanscomprises a reservoir nipple and that said second connecting meanscomprises a connecting nipple wherein the reservoir module supplies saiddispenser module with the drug liquid via said nipples.
 3. Systemaccording to claim 1 characterized in that said reservoir modulecomprises drug supplying means adapted to be coupled to the dispensermodule in order to supply the dispenser module with the drug from thereservoir module.
 4. System according to claim 1 characterized in thatsaid dispenser module is provided with a predetermined number of drugdelivery openings, wherein said predetermined number is at least two. 5.System according to claim 4 characterized in that the openings of thedispenser module are arranged on the part of the dispenser moduleadapted to be in contact with tissue.
 6. System according to claim 4 inthat the openings of the dispenser module are arranged along theperiphery of the dispenser module.
 7. System according to any of claim 4in that said predetermined number of delivery openings is four. 8.System according to any of claim 4 in that said predetermined number ofdelivery openings lies in the interval 10-30.
 9. Method ofadministrating a drug liquid to a patient using an implantable drugdelivery system according to of claim 1 characterized in that saidmethod comprising the following steps: i) choosing a dispenser moduleand a reservoir module having predetermined characteristics depending onthe prescribed therapy of the patient; ii) connecting the chosen modulesto each other; iii) implanting the system at a patient location wherethe drug should be administrated.
 10. Method according to claim 9characterized in that said method further comprising the following step:iv) filling or refilling the reservoir module with a drug liquid whennecessary.